Tumor-initiating activity of the bay-region dihydrodiols and diolepoxides of dibenz[a,j]anthracene and cholanthrene on mouse skin

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Abstract
The tumor-initiating activity of dibenz[a,j]anthracene, (.+-.)dibenz[a,j]anthracene-trans-3,4-diol and (.+-.)dibenz[a,j]anthracene-anti-3,4-diol-1,2-epoxide in mouse skin as examined and compared to that of cholanthrene, (.+-.)cholanthrene-trans-9,10-diol and (.+-.)cholanthrene-anti-9,10-diol-7,8-epoxide. The tumor-initiating activity of these compounds dissolved in acetone or in tetrahydrofuran (THF) was also compared. In acetone, dibenz[a,j]anthracene was a weak tumor initiator with maximal tumor yields of 1.27 and 3.00 per mouse at 400 and 800 nmol doses, respectively. At the 400 nmol dose, the diol of this compound was slightly more active than the parent compound while the tumorigenic activity of the diol-epoxide was significantly higher. The diol-epoxide was almost three times more active than the parent compound as a tumor-initiator. Cholanthrene was a moderate tumor-initiator with maximal tumor yields of 6.90 and 8.86 tumors per mouse at 200 and 600 nmol doses, respectively, after 20 weeks of promotion. At comparable doses, (.+-.)cholanthrene-trans-9,10-diol was .apprx. 50% as potent as cholanthrene as a tumor initiator whereas the diol-epoxide was only minimally active. Replacing the acetone with THF as solvent vehicle increased the tumor-initiating activity of cholanthrene-diol-epoxide; however, the parent compound still retained higher tumor-initiating activity than its bay-region diol-epoxide. The low tumorigenic activity of cholanthrene-diol-epoxide is thought to reflect the high chemical reactivity and low stability of this derivative, which may prevent it from penetrating to epidermal targets. In contrast, the bay-region diol-epoxide derivative of dibenz[a,j]anthracene appears to be stable enough to exert greater biologic activity when appplied to mouse skin.